Summary
1,2,3,4-Tetrahydroisoquinoline (TIQ) was identified in normal and parkinsonian human brains by gas chromatography-mass spectrometry (GC-MS). In human brain, N-methyl TIQ (NMTIQ) was formed by a N-methyltransferase in the cytosol fraction. The in vivo synthesis of NMTIQ was also confirmed in the brains of marmosets systematically administrated with TIQ. TIQ itself was not oxidized by monoamine oxidase, but NMTIQ was oxidized by both types A and B monoamine oxidase. The oxidative product, N-methylisoquinolinium ion (NMIQ+), inhibited enzymes participating in catecholamine metabolism, such as tyrosine hydroxylase, DOPA decarboxylase and monoamine oxidase. The uptake of NMIQ+ was mediated by the dopamine transport system. These data support our view that TIQ and its derivatives may be candidates of dopaminergic neurotoxin similar to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahy- dropyridine. Proc Natl Acad Sci USA 80: 4546–4550
Cohen G, Collins MA (1970) Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism. Science 167: 1749–1751
Collins MA (1980) Neuroamine condensations in human subjects. Adv Exp Med Biol 126: 87–102
D’Amato RJ, Lipman ZP, Snyder SH (1986) Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin. Science 231: 987–989
Ehringer H, Hornykiewicz O (I960) Verteilung von Noradrenalin und Dopamin (3- Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen System. Klin Wschr 24: 1236–1239
Hirata Y, Sugimura H, Takei H, Nagatsu T (1986) The effects of pyridinium salts, structurally related compounds of l-methyl-4-phenylpyridinium ion (MPP+), on tyrosine hydroxylation in rat striatal tissue slices. Brain Res 397: 341–344
Hirata Y, Minami M, Naoi M, Nagatsu T (1990) Studies on the uptake of N- methylisoquinolinium ion into rat striatal slices using high-performance liquid chromatography with fluorometric detection. J Chromatogr 503: 189–195
Javitch JA, D’Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 82: 2173–2177
Kiuchi K, Hagihara M, Hidaka H, Nagatsu T (1988) Effect of l-methyl-4-phenylpy- ridinium ion on tyrosine hydroxylase in rat pheochromocytoma PC12h cells. Neurosci Lett 89: 209–215
Kohno M, Ohta S, Hirobe M (1986) Tetrahydroisoquinoline and 1-methyl-tetrahy-droisoquinoline as novel endogenous amines in rat brain. Biochem Biophys Res Commun 140: 448–454
Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219: 979–980
Nagatsu T, Hirata Y (1987) Inhibition of the tyrosine hydroxylase system by MPTP, l-methyl-4-phenylpyridinium ion (MPP+) and the structurally related componds in vitro and in vivo. Eur Neurol 26 [Suppl 1]: 11–15
Nagatsu T, Yamaguchi T, Kato T, Sugimoto T, Matsuura S, Akino M, Nagatsu I, Iizuka R, Narabayashi H (1981) Biopterin in human brain and urine from controls and parkinsonian patients: application of a new radioimmunoassay. Clin Chim Acta 109: 305–311
Nagatsu T, Yoshida M (1988) An endogenous substance of the brain, tetrahydroisoquinoline, produces parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the nigrostriatal regions. Neurosci Lett 87: 178–182
Naoi M, Nagatsu T (1987) Quinoline and quinaldine as naturally occurring inhibitors specific for type A monoamine oxidase. Life Sci 40:1075–1082
Naoi M, Hirata Y, Nagatsu T (1987) Inhibition of monoamine oxidase by N-methylisoquinolinium ion. J Neurochem 48: 709–712
Naoi M, Takahashi T, Nagatsu T (1988) Effect of l-methyl-4-phenylpyridinium ion (MPP+) on catecholamine levels and activity of related enzymes in clonal rat pheochromocytoma PC12h cells. Life Sci 43: 1485–1491
Naoi M, Matsuura S, Parvez H, Takahashi T, Hirata Y, Minami M, Nagatsu T (1989a) Oxidation of N-methyl-l,2,3,4-tetrahydroisoquinoline into the N-methylisoqu- inolinium ion by monoamine oxidase. J Neurochem 52: 653–655
Naoi M, Matsuura S, Takahashi T, Nagatsu T (1989b) A N-methyltransferase in human brain catalyses N-methylation of 1,2,3,4-tetrahydroisoquinoline into N-methyl- 1,2,3,4-tetrahydroisoquinoline, a precursor of a dopaminergic neurotoxin, N- methylisoquinolinium ion. iJiochem Biophys Res Commun 161: 1213–1219
Naoi M, Takahashi T, Parvez H, Kabeya R, Taguchi E, Yamaguchi K, Hirata Y, Minami M, Nagatsu T (1989c) N-Methylisoquinolinium ion as an inhibitor of tyrosine hydroxylase, aromatic L-amino acid decarboxylase and monoamine oxidase. Neurochem Int 15: 315–320
Niwa T, Takeda N, Kaneda N, Hashizume Y, Nagatsu T (1987) Presence of tetrahy- droisoquinoline and 2-methyl-tetrahydroquinoline in parkinsonian and normal human brains. Biochem Biophys Res Commun 144: 1084–1089
Niwa T, Takeda N, Tatematsu A, Matsuura S, Yoshida M, Nagatsu T (1988) Migration of tetrahydroisoquinoline, a possible parkinsonian neurotoxin, into monkey brain from blood as proved by gas chromatography-mass spectrometry. J Chromatogr 452: 85–91
Niwa T, Takeda N, Sasaoka T, Kaneda N, Hashizume Y, Yoshizumi H, Tatematsu A, Nagatsu T (1989a) Detection of tetrahydroisoquinoline in parkinsonian brain as an endogenous amine by gas chromatography-mass spectrometry. J Chromatogr 491: 397–403
Niwa T, Yoshizumi H, Tatematsu A, Matsuura S, Nagatsu T (1989b) Presence of tetrahydroisoquinoline, a parkinsonism-related compound, in foods. J Chromatogr 493: 347–352
Niwa T, Yoshizumi H, Tatematsu A, Matsuura S, Yoshida M, Kawachi M, Naoi M, Nagatsu T (1990) Endogenous synthesis of N-methyl-l,2,3,4-tetrahydroisoquino- line, a precursor of N-methylisoquinolinium ion, in the brains of primates with parkinsonism after systemic administration of 1,2,3,4-tetrahydroisoquinoline. J Chromatogr 533: 145–151
Ohta S, Kohno M, Makino Y, Tachikawa O, Hirobe M (1987) Tetrahydroisoquinoline and 1-methyl-tetrahydroisoquinoline are present in the human brain: relation to Parkinson’s disease. Biomed Res 8: 453–456
Ogawa M, Araki M, Nagatsu I, Nagatsu T, Yoshida M (1989) The effect of 1,2,3,4- tetrahydroisoquinoline (TIQ) on mesencephalic dopaminergic neurons in C57BL6J mice: Immunohistochemical studies-tyrosine hydroxylase. Biogenic Amines 6: 427–436
Suzuki K, Mizuno Y, Yoshida M (1988) Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity and ATP synthesis by tetrahydroisoquinoline. Neurosci Lett 86: 105–108
Yoshida M, Niwa T, Nagatsu T (1990) Parkinsonism in monkeys produced by chronic administration of an endogenous substance of the brain, tetrahydroisoquinoline: the behavioral and biochemical changes. Neurosci Lett 119: 109–113
Zarranz de Ysern ME, Ordnez I (1981) Tetahydroisoquinolines: a review. Prog Neuro- psychopharmacol 5: 343–355
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer-Verlag/Wien
About this paper
Cite this paper
Naoi, M., Niwa, T., Yoshida, M., Nagatsu, T. (1991). Tetrahydroisoquinoline and its derivatives: the occurrence and the metabolism in the brain, and the effects on catecholamine metabolism. In: Nagatsu, T., Narabayashi, H., Yoshida, M. (eds) Parkinson’s Disease. From Clinical Aspects to Molecular Basis. Key Topics in Brain Research. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9146-0_7
Download citation
DOI: https://doi.org/10.1007/978-3-7091-9146-0_7
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-82272-2
Online ISBN: 978-3-7091-9146-0
eBook Packages: Springer Book Archive